This invention pertains to film-enrobed unitary-core products such as medicine tablets, to films and film compositions for making such products, and to methods and equipment for manufacturing such products. More specifically, within a presently preferred area of that field, the invention pertains to medicines and the like comprising cores of one-piece tablet nature in various geometrical forms which are enrobed in preferably digestible or erodable films applied to the cores separately from formation of the cores; the invention also pertains to gelatin-based and other films for enrobing such cores, to methods for enrobing such cores with such films, and to equipment for performing such methods to produce such products.
The pharmaceutical, vitamin and related industries have long used various ways to present their products to users in swallowable oral dosage forms, other than purely as liquids, so that persons using such products can use them conveniently and comfortably. Broadly, orally used non-liquid medicines and the like are provided in two general forms. One form is a tablet in which the dosage unit is a solid, hard swallowable shape comprised of the desired active ingredients compressed and formed with suitable binders into an integral article. Tablets, in their broadest sense, are available in many shapes and sizes. The other common solid dosage is a capsule in which the active ingredients occur in a flowable state (powder, liquid, paste or the like) and are encased in a digestible shell of a suitable shape and form which is swallowable. Variations exist within and between these two general forms. Thus, it is known to coat, as by dipping or spraying, tablet-type dosage units with gelatin or other materials to make them more palatable, easier to swallow, less prone to powder or to flake when handled in bottles, colored for eye appeal or identifiability, and longer lasting before active ingredients degrade, among other reasons. Capsule forms of such products occur as soft gelatin capsules, which commonly are of spherical or oblate spherical shape, and as hard gelatin capsules which commonly are of elongated round-ended cylindrical form and which are made in two pieces for assembly, with or without sealing, around the flowable fill material containing the desired active ingredients.
The portion of U.S. Pat. No. 4,820,524 entitled xe2x80x9cBack-ground of the Inventionxe2x80x9d (which portion is incorporated herein by reference) presents a comprehensive and good review of hard gelatin encapsulated medicines and the like, and of certain forms of solid medicaments having spray-applied or dip-applied gelatin coatings. That review is presented as an introduction to the invention of that patent which is a caplet (a tablet shaped to resemble a hard gelatin capsule) dipped first at one end and then at its other end in liquid gelatin to form, upon drying of the gelatin, a gelatin coating fully enclosing the preformed, base solid caplet. The text of that review notes that, because of the problem of tampering which had been experienced with hard gelatin capsule products, many manufacturers of such products withdrew them from the market in favor of other forms of active-ingredient presentment, notably caplets. The withdrawal of hard gelatin encapsulated products from the market left those manufacturers with idle machines for making hard gelatin capsules, a situation which U.S. Pat. No. 4,820,524 addressed by its descriptions of how such machinery could be modified to produce an at least twice-dipped, gelatin-coated caplet form of medicine. The resulting final product can be colored uniformly, or it can be colored differently at its opposite ends by differently tinting the gelatin baths into which each of the opposite ends of the caplet preform is dipped at least once. A number of advantages of such products over hollow hard gelatin capsules and over pan-coated tablets are noted in U.S. Pat. No. 4,820,524 at column 11, lines 19 et seq.
In its detailed description, namely, at column 10, lines 47 et seq., U.S. Pat. No. 4,820,524 notes that the dipping of preformed caplets into wet gelatin baths can have disadvantageous effects, and that precoating of the caplet with a sealant, such as a moisture barrier, can be useful.
While the procedures described in U.S. Pat. No. 4,820,524 for producing at least twice-dipped, gelatin-coated caplets are relatively simple, the machinery required for high-volume implementation of those procedures is quite complex, extensive and expensive. Also, those procedures and that machinery are not well suited for handling solid medicament preforms in shapes other than caplet shape.
In the context of soft gelatin capsules and the procedures and equipment for their manufacture, there have occurred descriptions of ways to produce approximations of gelatin coated tablets. The usual soft encapsulated gelatin product is one in which a flowable fill material (powder, paste or liquid) containing the desired active ingredient is pumped under pressure into place where two films of soft elastic gelatin are brought together between rotating or reciprocating dies with which the films are in contact. The dies have cavities formed in their surfaces. The pumping of fill material between the plastic gelatin films is carefully timed in synchronism with die movement so that a metered amount of fill is discharged between the films to cause the films to bulge into adjacent opposed die cavities. The films come together around a controlled amount of fill as the dies continue to move and the films are then sealed together by applying pressure and/or heat at the dies which then coact to cut the films at the seal. The then fully-enclosed-by-gelatin fill dosage quantity separates from the films as a discrete article. That article may then be washed to remove film lubricants (such as mineral oil) and then dried to provide the finished product which is suitably packaged for sale.
U.S. Pat. No. 2,663,128 (1953), U.S. Pat. No. 2,697,317 (1954), and U.S. Pat. No. 2,775,080 (1956), all issued to F. E. Stirin and A. S. Taylor as assignors to American Cyanamid Company, describe complex procedures and equipment in which a suitable active ingredient powder is formed into a soft pellet. The pellet is transferred by a vacuum holding mechanism into registry with and dispensed into a cup-like depression formed by vacuum in a plastic gelatin film. The cup-like depression can also contain a liquid. Thereafter, the film which defines the loaded depression is moved into contact with a second gelatin film which is sealed across the depression. The loaded and sealed depression is cut from the adhered pair of films, and the product then self-adjusts its shape to a desired tablet, sphere, or capsule-like shape, after which it is processed similarly to a conventional soft encapsulated gelatin capsule.
More recently (Packaging Technology, March/April 1987, Vol 17, No. 2, pp. 4, 7 and 16), equipment and methods for encasing a pair of half-dose softly-compacted tablet-like preforms between converging soft elastic gelatin films have been described. So far as is known, such equipment was not successfully built and operated.
These earlier descriptions of adaptations of soft elastic gelatin encapsulated tablet-like products in the Stirin et al patents and the Packaging Technology article teach that the tablet is formed as a soft preform and that such formation occurs in the same machinery which encloses the preform between two soft gelatin films. Such teaching is inconsistent with the actual development and present state of the industry which produces soft elastic gelatin capsules. That industry is based upon substantial investments of capital, time and human experience and is comprised of firms which are essentially packagers of products of others. Those firms either receive the flowable active-ingredient fill materials produced by others such as pharmaceutical manufacturers or vitamin compounders, or they formulate the fill material under the control of and in compliance with the specifications of others. They then pump that flowable material into place between two soft gelatin films in machines which they own and operate under controlled conditions. They then deliver the finished capsules in bulk back to their customers who package and market the capsules under their own names. Present reality is that tablet manufacture is one industry and soft elastic gelatin capsule manufacture is a separate and distinct industry. Members of one industry are reluctant to invest the capital and other resources necessary to acquire the equipment and skills, and also the risks and responsibilities, present in the other industry; they prefer, for sound reasons, to keep the industries separate and to trade between the industries in the manner described. The teachings of the Stirin et al patents and the Packaging Technology article call for a blending of those separate industries. That blending has not occurred and likely will not occur for the reasons noted. A need exists for gelatin enrobed tablets which are free of the problems noted in U.S. Pat. No. 4,820,524 occasioned by the necessarily high temperature and high moisture content of gelatin baths into which caplets can be dipped. A need exists for technology useful to enable members of the soft elastic gelatin capsule industry to apply their resources and talents to the manufacture of gelatin enrobed tablets without requiring that industry to, in effect, blend with the tablet manufacturing industry. A need exists for improved procedures and equipment which are compatible with the existing investments and skills in the soft elastic gelatin capsule industry, and which will enable members of that industry to receive from the tablet industry tablets of various sizes and shapes, to individually package those tablets in soft films, and to deliver such packaged tablets back to the tablet industry for market packaging and distribution. A need exists for a way for the soft elastic gelatin capsule industry to support and service the tablet manufacturing industry in providing improved film enrobed tablets without disturbing the existing working relationships between those industries. This invention addresses those needs and, in so doing, provides an improved tablet product.
Previously published documents considered in the development and patenting of this invention include the following documents:
U.S. Pat. Nos. 2,296,294, 2,663,128, 2,697,317, 2,775,080, 2,836,291, 3,228,789, 4,281,763, and 4,820,524, and Packaging Technology, Vol. 17, No. 2, March/April 1987, pages 4, 7 and 16.
Terminology
The following description of this invention and the appended claims use the terms xe2x80x9ccoatxe2x80x9d, xe2x80x9ccoatingxe2x80x9d, xe2x80x9cenrobexe2x80x9d, and xe2x80x9ccoveringxe2x80x9d to refer to and to describe the enclosing layer which the practice of this invention provides around a medicine tablet, for example. In that context, unless the specific usage indicates otherwise, the words xe2x80x9ccoatxe2x80x9d and xe2x80x9ccoatingxe2x80x9d are used in the same sense and meaning as xe2x80x9ccoverxe2x80x9d and xe2x80x9ccoveringxe2x80x9d and not in the sense of an outer tablet layer which is formed incrementally over some period of time on a tablet core by techniques known in the pharmaceutical industry as xe2x80x9cpan coatingxe2x80x9d or their equivalents.
This invention provides an improved dosage form, among other kinds of products, in which a solid tablet preform or core is fully enrobed in soft elastic film material, such as a gelatin film, in a relatively dry state and at relatively low temperature. Formation of the tablet can occur at times and at places segregated from the time and place where the tablet is film-enrobed. The substantially dry and low temperature nature of the tablet enrobing process is important to the integrity and life of the active ingredients in the tablet. The film enrobing the tablet can tightly bond to the tablet so that, especially when the film is distinctively colored, the enrobed tablet is tamper-evident. The enrobing films can be colored to produce monocolored or bicolored enrobed tablets. The enrobed tablets can be further processed to have enteric coatings so that when swallowed, the tablets pass through the stomach and dissolve in the intestines; the film enrobing the tablet can protect the tablet from undesirable reactions with constituents of the enteric or other coatings applied over the film. The enrobed tablet can be so enrobed as to have significantly more strength and resistance to breakage when handled or subsequently processed than the unenrobed tablet.
Generally speaking, according to one aspect of the invention, this invention provides a new article of manufacture comprised of a unitary article preform of selected shape and size which is fully enrobed between two layers of applied elastic film material of selected thickness and composition, which layers substantially conform to the contours of the preform and which are sealed to each other along a single line encircling the preform and lying substantially in a common plane. The film layers, when applied to the preform, exhibit substantially low water activity and have an elastic plastic character.
A presently preferred such article of manufacture is one in which the preform is a tablet of selected size and shape containing a desired amount of at least one selected active ingredient. The film material applied in tablet-enrobing manner to the tablet is a gelatin-base film so formulated that, as applied to and sealed around the tablet, it conforms tightly to the tablet contours and bonds securely to the tablet surfaces, is colored differently from the tablet, and dries to a hard state. The resulting product is stronger than the preform itself and provides a readily visible indication of efforts to remove the enrobing film from the tablet, whereby the enrobed tablet is tamper-evident.